CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome

Ample evidence indicates that codon usage bias regulates gene expression. How viruses, such as the emerging mosquito-borne Chikungunya virus (CHIKV), express their genomes at high levels despite an enrichment in rare codons remains a puzzling question. Using ribosome footprinting, we analyze transla...

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Detalles Bibliográficos
Autores: Jungfleisch, Jennifer, 1986-, Böttcher, René, Talló Parra, Marc, 1992-, Pérez Vilaró, Gemma, 1985-, Merits, Andres, Novoa, Eva Maria, Díez Antón, Juana, 1962-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/54063
Acceso en línea:http://hdl.handle.net/10230/54063
http://dx.doi.org/10.1038/s41467-022-31835-x
Access Level:acceso abierto
Palabra clave:Methylation
tRNAs
Viral infection
Virus–host interactions
Descripción
Sumario:Ample evidence indicates that codon usage bias regulates gene expression. How viruses, such as the emerging mosquito-borne Chikungunya virus (CHIKV), express their genomes at high levels despite an enrichment in rare codons remains a puzzling question. Using ribosome footprinting, we analyze translational changes that occur upon CHIKV infection. We show that CHIKV infection induces codon-specific reprogramming of the host translation machinery to favor the translation of viral RNA genomes over host mRNAs with an otherwise optimal codon usage. This reprogramming was mostly apparent at the endoplasmic reticulum, where CHIKV RNAs show high ribosome occupancy. Mechanistically, it involves CHIKV-induced overexpression of KIAA1456, an enzyme that modifies the wobble U34 position in the anticodon of tRNAs, which is required for proper decoding of codons that are highly enriched in CHIKV RNAs. Our findings demonstrate an unprecedented interplay of viruses with the host tRNA epitranscriptome to adapt the host translation machinery to viral production.